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Head and Neck Cancers

Head and neck cancers are malignancies arising in the upper aerodigestive tract (this includes: lip, tongue, salivary glands, mouth, oropharynx, nasopharynx, hypopharynx, nasal cavity, and larynx). Laryngeal (voice-box) cancer is the most frequent type, accounting for about a quarter of head and neck cancers.

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Laryngeal Cancer
Hypopharyngeal Cancer
Nasopharyngeal Cancer
Oropharyngeal Cancer
Oral Cancer
Salivary Gland Cancer
Tracheal (windpipe) Cancer
Molecular Biology of Head and Neck Cancers
Head and Neck Cacer Resources
Latest Research Publications

Head and Neck Cacer Resources (16 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Houle A, Mandel L
Diagnosing the Parotid Lipoma. Case Report.
N Y State Dent J. 2015; 81(3):48-50 [PubMed] Related Publications
The clinical features of the rarely reported and diagnostically challenging parotid gland lipoma are described. Presurgical diagnosis is aided by CT scan imaging.

Philipone E, Bhagat G, Alobeid B
Oral Cavity Lymphoid Neoplasms. A Fifteen-Year Single Institution Review.
N Y State Dent J. 2015; 81(3):44-7 [PubMed] Related Publications
Although relatively rare, lymphomas can and do present within the oral cavity and can represent either the initial presentation or secondary involvement in the setting of systemic disease. Our objective was to conduct a retrospective search of the surgical pathology database at our institution to review all oral biopsy specimens diagnosed as either a lymphoma or plasma cell neoplasm over the past 15 years. Based on our search, we identified 47 cases. We report here the type of neoplasm, location, patient age and gender, and available pertinent clinical information.

Umair A, Tarakji B, Ibrahim A, et al.
Quantitative study of epigenetic signature in head and neck squamous cell carcinoma.
Turk J Med Sci. 2015; 45(2):372-86 [PubMed] Related Publications
BACKGROUND/AIM: The aberrant upregulation of Forkhead box protein M1 (FOXM1) plays a fundamental role in cancer initiation by perturbing stem cell differentiation. This study aims to investigate the role of FOXMI in epigenetic modification and gene expression of target genes in primary human oral keratinocytes, squamous cell carcinoma cell lines, and head and neck squamous cell carcinoma (HNSCC) tissue biopsies.
MATERIALS AND METHODS: A genome-wide promoter methylation microarray was used to compare HNSCC cell line (n = 8), primary human oral keratinocytes (NOK; n = 8) transduced with FOXM1 and EGFP, and HNSCC tissue biopsies (n = 3). Seventeen Foxm1B- induced differentially methylated genes were shortlisted. An absolute quantitative polymerase chain reaction was used to validate the differential promoter DNA methylation of each candidate gene induced by FOXML. These results were compared with the methylation status and altered gene expressions of candidate genes in a panel of genomic DNA and messenger RNA (mRNA) samples previously extracted from HNSCC tissue biopsies.
RESULTS: The results were consistent with our hypothesis, showing that aberrant. upregulation of FOXM1 expression in in vitro primary NOK induces a global hypomethylation pattern similar to the HNSCC cell line and has an inverse correlation with in vivo mRNA expression levels of HNSCC tissue biopsy.
CONCLUSION: Such epigenetic changes have tremendous clinical potential as biomarkers for early cancer detection and therapeutic interventions.

Hsiao CL, Tsai YH, Lin SK
Massive Epistaxis from Internal Carotid Pseudoaneurysm during Acute Ischemic Stroke in a Patient with Nasopharyngeal Carcinoma.
Acta Neurol Taiwan. 2014; 23(3):113-8 [PubMed] Related Publications
PURPOSE: Carotid blowout syndrome due to rupture of internal carotid artery pseudoaneurysm in NPC patients with prior neck radiation is an uncommon but life-threatening complication. Concomitant carotid stenosis with ischemic stroke and carotid rupture from pseudoaneurysm is rare.
CASE REPORT: A 71-year-old man had a history of NPC treated with radiation therapy 26 years ago. He was admitted to the hospital because of minor ischemic stroke and tarry stool. The carotid duplex sonography disclosed severe stenotic lesion in the proximal right internal carotid artery. A subsequent recurrent stroke on day three associated with nasal cavity bleeding resulted in an endotracheal intubation. Another episodic of massive epistaxis occurred on day 10 caused hypovolemic shock. Pseudoaneurysm of the left internal carotid artery was found by emergent angiography and was immediately obliterated by endovascular treatment with microcoils and glue.
CONCLUSION: Carotid blowout syndrome in NPC patients during acute ischemic stroke warrants further cervical angiographic study. Endovascular treatment provides immediate hemostasis and obliteration of ICA pseudoaneurysm.

Andrei R, Zurac S, Socoliuc C, et al.
Problems of Differential Diagnosis in Melanoma Arising from Blue Naevus.
Rom J Intern Med. 2015 Jan-Mar; 53(1):95-101 [PubMed] Related Publications
Melanoma arising from blue naevus is an exceedingly rare variant of melanoma. Most of the cases are located in head and neck area, with scalp the most affected site. This type of melanoma develops on blue naevus or resembles blue naevus, most frequently cellular blue naevus. We present the case of a 52 years old female diagnosed with a pigmented melanoma of the scalp, with maximum tumoral thickness of 6.8 mm and invasion of the hypodermis, highly resembling cellular blue naevus. All criteria of malignancy were present: prominent nuclear pleomorphism, infiltrative pattern, tumoral necrosis, high mitotic rate (11 mitoses/mm2) with atypical mitosis and high Ki67 index. No lymph node or distant metastases were identified at presentation. Because of the rarity of cases, histopathological diagnosis can be difficult, differential diagnosis with blue naevi, atypical blue naevi or metastatic melanoma being the most challenging problems. Prognosis is given by tumoral thickness, frequently being more than 4 mm.

Kalavrezos N, Scully C
Mouth Cancer for Clinicians. Part 1: Cancer.
Dent Update. 2015; 42(3):250-2, 255-6, 259-60 [PubMed] Related Publications
A MEDLINE search early in 2015 revealed more than 250,000 papers on head and neck cancer; over 100,000 on oral cancer; and over 60,000 on mouth cancer. Not all publications contain robust evidence. We endeavour to encapsulate the most important of the latest information and advances now employed in practice, in a form comprehensible to healthcare workers, patients and their carers. This series offers the primary care dental team, in particular, an overview of the aetiopathogenesis, prevention, diagnosis and multidisciplinary care of mouth cancer, the functional and psychosocial implications, and minimization of the impact on the quality of life of patient and family. Clinical Relevance: This article offers the dental team a simplified overview of carcinogenesis, and a review of cancers that affect the oral region.

Kalavrezos N, Scully C
Mouth cancer for clinicians. Part 2: Epidemiology.
Dent Update. 2015; 42(4):354-6, 358-9 [PubMed] Related Publications
A MEDLINE search early in 2015 revealed more than 250,000 papers on head and neck cancer; over 100,000 on oral cancer; and over 60,000 on mouth cancer. Not all publications contain robust evidence. We endeavour to encapsulate the most important of the latest information and advances now employed in practice, in a form comprehensible to healthcare workers, patients and their carers. This series offers the primary care dental team, in particular, an overview of the aetiopathogenesis, prevention, diagnosis and multidisciplinary care of mouth cancer, the functional and psychosocial implications, and minimization of the impact on the quality of life of patient and family. Clinical Relevance: This article offers the dental team an overview of the changing epidemiology of, and increases in mouth cancer.

Ali R, Altaie A, Nattress B
Rehabilitation of oncology patients with hard palate defects. Part 1: The surgical planning phase.
Dent Update. 2015; 42(4):326-8, 331-2, 335 [PubMed] Related Publications
This article is the first in a series of three papers that will discuss the conventional non-implant retained prosthodontic rehabilitation of oncology patients with surgically acquired hard palate defects. In this first paper, the dental challenges posed by the oncology patients will briefly be discussed. The interface between the specialist restorative dentist and the maxillofacial surgeon when planning the conventional dental rehabilitation of an oncology patient with a hard palate defect will be discussed in detail. Clinical Relevance: To highlight the importance of the restorative dentistry/surgical interface when planning a treatment for a patient requiring a maxillectomy and conventional obturation.

Sotirović J, Šuljagić V, Baletić N, et al.
Risk factors for surgical site infection in laryngeal cancer surgery.
Acta Clin Croat. 2015; 54(1):57-64 [PubMed] Related Publications
Surgical site infection (SSI) is a significant factor of morbidity and mortality in patients surgically treated for laryngeal carcinoma. The aim of this prospective study in 277 patients was to determine the incidence of SSI in patients surgically treated for laryngeal squamous cell carcinoma and to identify risk factors for development of SSI. Patients with previous chemotherapy and/or radiotherapy were excluded. All patients had tracheostomy postoperatively and received antibiotic prophylaxis with cephalosporin, aminoglycoside and metronidazole. The overall incidence of SSIs in our cohort was 6.5% (18 patients): 4 (22.22%) patients with superficial infections, 11 (61.11%) with deep infections and 3 (16.66%) with organ-space infections. The remaining infections included pneumonia (1 case) and Clostridium difficile colitis (2 cases). The median hospital stay in patients having developed SSIs was longer than in those without SSIs (33.5 vs. 16 days, p < 0.001). By using univariate analysis American Society of Anesthesiologists score > 3, duration of surgery longer than 120 minutes and National Nosocomial Infections Surveillance risk index > 1 were found to be significantly associated with the occurrence of SSI. Age, sex, body mass index, history of smoking, underlying diabetes and preoperative length of stay were found not to be associated with SSI. The most frequently isolated microorganism was Klebsiella spp.

Vučemilo L, Znaor T, Kuliš T, et al.
Thyroid cancer incidence and mortality trends in Croatia 1988-2010.
Acta Clin Croat. 2015; 54(1):30-7 [PubMed] Related Publications
The aim of our study was to describe and interpret national trends in thyroid cancer in Croatian men and women during the 1988-2010 period, to better understand the incidence and mortality trends in comparison with other populations, and to determine the proportion of certain histologic subtypes of thyroid cancer and their impact on these trends. Using information from the Croatian National Cancer Registry and WHO Mortality Database, we estimated trends in the age-standardized incidence and mortality rates by joinpoint regression analysis. Thyroid cancer incidence increased in both women and men during the study period, with the estimated annual percent change (EAPC) of 6.4% and 5.5%, with no joinpoints identified. A significant decrease in mortality (EAPC-2.1%) was observed in women, while in men mortality rates decreased nonsignificantly (EAPC-1.3%). A statistically significant incidence increase was observed only for papillary carcinomas with annual incidence increase by 6.7% for women and 7.9% for men. During the study period, thyroid cancer showed an incidence increase in Croatia with persistent and steady decrease in mortality in women and statistically nonsignificant decrease in mortality in men. The increase in papillary carcinomas led to the thyroid cancer incidence increase and also affected the thyroid cancer mortality decrease in women. The trends observed are similar to those in other European countries and require additional analysis to determine all factors that have an effect on them.

Vega-Vázquez MA, Gonzalez-Rodriguez L, Santiago-Rodríguez EJ, et al.
Quality of life-in patients with differentiated thyroid cancer at the general endocrinology clinics of the University Hospital of Puerto Rico.
Bol Asoc Med P R. 2015 Jan-Mar; 107(1):25-31 [PubMed] Related Publications
UNLABELLED: Differentiated thyroid cancer (DTC) can compromise the quality of life of patients. Our purpose is to investigate if the quality of life, in a cohort of patients in Puerto Rico, is affected by the diagnosis and/or treatment modalities received for DTC.
METHODS: This is a cross-sectional study of 75 subjects with DTC. A Spanish version of the University of Washington Quality of Life Questionnaire was used, including multiple aspects of physical and social functioning. Descriptive and bivariate analysis between domain scores and variables of interest were performed.
RESULTS: 82.7% of the patients reported that their health was the same or better than it was before treatment. The mean composite score obtained was 82.3, reflecting an overall little effect on quality of life. Patients diagnosed with DTC at an age of > or =45 years reported a significantly better score on the pain domain when compared with those diagnosed earlier (p < 0.05). Patient who received >150 mCi of radioiodine had a tendency towards a worse score on the same domain (p = 0.05).
CONCLUSIONS: Our cohort reported an overall minimal effect on the quality of life of patients with DTC. Future treatment strategies should include periodic quality of life evaluations, in order to tailor therapy in this growing population.

Yarlagadda BB, Hatton E, Huettig J, Deschler D
Patient and staff perceptions of social worker counseling before surgical therapy for head and neck cancer.
Health Soc Work. 2015; 40(2):120-4 [PubMed] Related Publications
Patients who undergo surgical therapy for head and neck cancer often face a tremendous challenge involving considerable psychological distress and impaired social functioning. These difficulties are often compounded by logistical difficulties such as transportation, financial assistance, and continuity of care after the acute hospitalization. Social workers have a unique opportunity to address the psychosocial and logistical issues facing these patients through preadmission counseling and coordination. The study reported in this article aimed to assess the effect of preadmission counseling for patients planning to undergo major surgical therapy for head and neck cancer. Ten patients who received preadmission counseling were surveyed to ascertain the utility of it in regard to multiple social and logistical factors. Comparisons were made with patients who did not receive such counseling. Staff perceptions were likewise obtained. The surveys indicated that preadmission counseling helped in regard to improving peri-admission support and access to financial and logistical resources, and lowered levels of anxiety during admission. Areas of potential improvement were identified, including addressing substance abuse issues in a timely manner.

Lee CC, Ho HC, Su YC, et al.
MCP1-Induced Epithelial-Mesenchymal Transition in Head and Neck Cancer by AKT Activation.
Anticancer Res. 2015; 35(6):3299-306 [PubMed] Related Publications
AIM: To explore whether monocyte chemotactic protein-1 (MCP1) is associated with the epithelial-mesenchymal transition (EMT) and neck metastases in head and neck cancer (HNC).
MATERIALS AND METHODS: MCP1 and its related protein were evaluated using western blotting, and a migration assay for HNC cell lines. Thirty-five patients with HNC were recruited for the evaluation of MCP1 expression and pathologically-proven neck metastases from their tissue specimens.
RESULTS: MCP1 changed the phenotype of OML-1 cells to a spindle shape, with increased mobility. In OML3 cells, MCP1 knockdown with siRNA blocked EMT. Activation of protein kinase B (AKT) was positively associated with the EMT phenotype, and this transition was abrogated with a phosphoinositide 3 kinase (PI3K) inhibitor. By comparing clinical outcomes, the histological MCP1 score was associated with pathological neck metastases (p=0.027).
CONCLUSION: The overexpression of MCP1 in HNC cells may partially induce EMT through the AKT pathway. A high cellular expression of MCP1 was associated with pathological neck metastases.

Hakelius M, Saiepour D, Göransson H, et al.
Differential Gene Regulation in Fibroblasts in Co-culture with Keratinocytes and Head and Neck SCC Cells.
Anticancer Res. 2015; 35(6):3253-65 [PubMed] Related Publications
BACKGROUND: While carcinoma-associated fibroblasts (CAFs) support tumorigenesis, normal tissue fibroblasts suppress tumor progression. Mechanisms behind conversion of fibroblasts into a CAF phenotype are largely unrevealed.
MATERIALS AND METHODS: Transwell co-cultures with fibroblasts in collagen gels and squamous-cell carcinoma (SCC) cells or normal oral keratinocytes (NOKs) in inserts. Differences in fibroblast global gene expression were analyzed using Affymetrix arrays and subsequent functional annotation and cluster analysis, as well as gene set enrichment analysis were performed.
RESULTS: There were 52 up-regulated and 30 down-regulated transcript IDs (>2-fold, p<0.05) in fibroblasts co-cultured with SCC compared to NOKs. Functional analysis demonstrated an enrichment of collagen-related genes. There were similarities with gene sets reflecting a non-specific, innate-type response with activation of both interferon pathways and connective tissue turnover.
CONCLUSION: There were distinct differences in fibroblast gene expression between the co-culture types. Many were in genes related to an innate-type of response and to connective tissue turnover.

Scott A
Non-sting barrier cream in radiotherapy-induced skin reactions.
Br J Nurs. 2015 May 28-Jun 10; 24(10):S32, S34-7 [PubMed] Related Publications
A pilot evaluation was undertaken in 13 patients with head and neck cancer exploring the use of a non-sting barrier film (Sorbaderm(®,) Aspen Medical Europe Ltd). The Society of Radiographers issued guidance in 2013 warning their members that the use of Aqueous cream for moisturising the skin during radiotherapy was potentially harmful. Patients were monitored over a period of 6 weeks and the aim was to explore whether applying non-sting barrier cream provided a protective barrier that did not impair treatment, slowed or prevented skin damage, was easy and simple to apply for patients and carers, improved quality of life for patients during radiotherapy or aided healing. There appeared to be a delay in skin breakdown in this evaluation from week 3 to week 4 and then only mild pain was recorded and with a maximum Radiation Therapy Oncology Group scale of 2.5 in the patient that had combined chemotherapy and radiotherapy. The patients' overall assessment demonstrated that the use of non-sting barrier cream provided symptom relief in both dry, tightening and itching of the skin associated with radiotherapy. All except one patient found the cream easy to apply. The head and neck nursing team rated the product as 'good' to 'very good'.

Kresić S, Veselinović M, Mumović G, Mitrović SM
Possible factors of success in teaching esophageal speech.
Med Pregl. 2015 Jan-Feb; 68(1-2):5-9 [PubMed] Related Publications
INTRODUCTION: Well-established esophageal voice and speech is the most human-like form of communication of laryngectomized patients.
MATERIAL AND METHODS: The study sample consisted of 28 patients of the Department of Ear. Nose and Throat, Clinical Center of Vojvodina in Novi Sad. All patients underwent total laryngectomy because of laryngeal cancer previously confirmed. The patients were divided into two groups based on the success of mastering esophageal voice and speech, group I being successful and group 2 being unsuccessful. Results. All patients were subjected to total laryngectomy and had their hyoid bone removed (100%). Esophageal speech was rated excellent afid good in 71% and 29% of patients from group 1, respectively. There was no significant difference between the successful (group 1) and unsuccessful group (group 2) in time when teaching began (chi2=5.14, p=0.023). Neither was there a statistically significant difference between these two groups regarding the methods applied in teaching esophageal. speech (chi2 = 2.02, p=0.155, which is greater than 0.05).
CONCLUSION: The effectiveness of teaching esophageal speech depends significantly on the motivatidn of the patients. It was found that the patients who mastered esophageal speech successfully had'been learning it longer than those who did not master it. The success in mastering esophageal speech did not depend on whether the patients were trained individually or collectively, whereas neither method of training was successful in group 2.

Liu YC, Lee KW, Sheu RJ
Comparing dose rates near a radioactive patient evaluated using various source models: point, line, cylinder, and anthropomorphic phantoms.
Health Phys. 2015; 109(1):69-77 [PubMed] Related Publications
This study investigated radiation exposures from nuclear medicine patients by systematically comparing the dose rates calculated using various source models, ranging from simplified point, line, and cylinder sources to high-quality anthropomorphic phantoms. Three widely used radionuclides, (99m)Tc, (18)F, and I(131), were considered in these source models with uniform or organ-dependent distributions. Conducting Monte Carlo simulations with anthropomorphic phantoms is a realistic but time-consuming approach. The point source model is simple but too conservative, overestimating dose rates by approximately a factor of 2 at a distance of 30 cm and by 30-40% at 1 m. Both the line and cylinder source models provided improved estimates, reducing the overestimation of dose rates to 10-20% at distances of interest. The line source model was comparable to the cylinder source model because of the offset of two competing effects (i.e., attenuation and buildup) caused by the source volume. The influence of various photon energies and cylinder sizes on the result of compensating errors was examined to evaluate the effective range of the line source model. The line source model, which is relatively easy to implement and predicts slightly conservative dose rates, is considered the most practical method for calculating dose rates near radioactive patients. An application of the line source model to 51 post-thyroidectomy patients in Taiwan was demonstrated. The consistency between calculations and measurements was satisfactory after considering the room-scattering effect.

Koc M, Aktimur R, Kagan Gokakin A, et al.
Expression of FHIT, p16, p53 and EGFR as prognostic markers in thyroid tumors of uncertain malignant potential.
J BUON. 2015 Mar-Apr; 20(2):567-72 [PubMed] Related Publications
PURPOSE: Thyroid tumors of uncertain malignant potential (TT-UMP) constitute a relatively new diagnosis. The purpose of this study was to analyze the relationship between immunohistochemical panels, prognostic parameters and TT-UMP.
METHODS: Group I was composed of patients diagnosed as differentiated thyroid carcinoma (DTC) and Group II of patients diagnosed as TT-UMP. The prognostic scores of patients were calculated using data according to the well-known prognostic scoring systems MACIS, AMES, AGES. Evaluations of antibodies were based on the presence of nuclear staining for p16 and p53, membranous and cytoplasmic staining for epidermal growth factor receptor (EGFR) and cytoplasmic staining for fragile histidine triad (FHIT).
RESULTS: Statistically significant difference was noted (p< 0.05) between Group I and Group II according to MACIS and AMES. No statistical difference was found in terms of immunostaining between groups when stained with p16, p53 and FHIT. On the other hand, in Group II a moderate positive correlation was detected between MACIS and EGFR.
CONCLUSION: According to our findings p53 was not important in tumor genesis at early stages in well-differentiated thyroid carcinomas and p16 loss of expression could be used as a finding to help in difficult microscopic diagnosis. TT-UMP is a gray zone of lesions requiring specific therapeutic procedures and postoperative follow-up. A positive correlation was detected between EGFR and TT-UMP, leading to assume that this situation could be used as a new tool in the follow-up of these patients in the future.

Inic Z, Inic M, Jancic S, et al.
The relationship between proliferation activity and parathyroid hormone levels in parathyroid tumors.
J BUON. 2015 Mar-Apr; 20(2):562-6 [PubMed] Related Publications
PURPOSE: This article examines as to whether the Ki-67 index may be useful as a marker for cell proliferation, as well as to whether Ki-67 immunohistochemical expression and parathyroid hormone (PTH) levels are useful in distinguishing between parathyroid carcinoma (PC) and adenoma.
METHODS: A retrospective analysis of 50 patients (10 with PC and 40 with adenoma) who had been previously diagnosed with primary hyperparathyroidism (PHPT) was conducted. Normal parathyroid glands served as the control group. Immunostaining of Ki-67 was estimated through image analysis and the results were statistically analyzed.
RESULTS: Ki-67 was higher in PC patients (median 785.15) compared to adenoma patients (median 297.41; Mann-Whitney U-test p<0.001). ROC analysis confirmed that Ki-67 has a positive predictive marker in diagnosing cancer. Mann-Whitney U-test confirmed a highly statistically significant difference in the preoperative PTH levels between the PC and adenoma group (p <0.001). The PTH serum preoperative level was higher in PC patients (median 1721) than in those with adenoma (median 189.5). A highly significant correlation was also found between Ki-67 and preoperative PTH levels (p <0.001).
CONCLUSION: A higher rate of cellular proliferation was noted in malignant tumors as compared to benign tumors. Moreover, the expression profile of Ki-67 and high PTH levels in this study indicates a role for them as potential markers of malignancy.

Mutlu P, Mutlu M, Yalcin S, et al.
Detection of XRCC1 gene polymorphisms in Turkish head and neck squamous cell carcinoma patients: a comparative analysis with different populations.
J BUON. 2015 Mar-Apr; 20(2):540-7 [PubMed] Related Publications
PURPOSE: X-ray repair cross-complementing (XRCC1) is one of the most important genes for the maintenance of genomic integrity and protection of cells from DNA damage. Although tobacco and alcohol consumption are the major risk factors for the development of head and neck squamous cell carcinoma (HNSCC), sequence variation in XRCC1 gene may alter HNSCC susceptibility. Reports on the relationship between HNSCC and polymorphisms in XRCC1 gene have been inconsistent so far. The aim of this study was to investigate the association of XRCC1 Arg194Trp and Arg399Gln single nucleotide polymorphisms (SNP), smoking and alcohol consumption with the risk of HNSCC in Turkish population and also to compare to these results with the ones from both Turkish and different populations in the literature. The frequencies of Arg194Trp and Arg399Gln SNPs were studied in 55 HNSCC and 69 healthy individuals.
METHODS: Genomic DNA was isolated from peripheral blood and SNP was genotyped by PCR-RFLP method.
RESULTS: The genotype and allele frequencies of both polymorphisms were not statistically different between the HNSCC and control groups. On the other hand, smoking and chronic alcohol consumption were associated with risk of HNSCC, but there was no association between Arg194Trp, Arg399Gln polymorphisms, smoking and alcohol consumption in HNSCC cases.
CONCLUSION: These results indicate that both Arg194Trp and Arg399Gln polymorphisms were not associated with the development of HNSCC in Turkish population. In addition, the allele frequencies of polymorphisms were in line with other Turkish population results that were studied previously. However, compared to different populations, there were marked differences in allele frequencies.

Gumusay O, Ozet A, Buyukberber S, et al.
Factors predicting the development of distant metastases in patients with head and neck squamous cell carcinoma: A retrospective study from a single centre.
J BUON. 2015 Mar-Apr; 20(2):521-6 [PubMed] Related Publications
PURPOSE: The presence of distant metastases (DMs) after the initial treatment of head and neck squamous cell carcinoma is associated with a poor outcome. The incidence of DMs in head and neck cancer is about 4-26%. The purpose of this study was to evaluate the prevalence of distant metastases and the factors predicting the development of DMs.
METHODS: Between January 2000 and December 2010, 292 patients with head and neck squamous cell carcinoma were included in this study.
RESULTS: Thirty three patients (11.3%) developed local recurrences, 27 patients (9.2%) developed DMs. The median post DMs survival was 23.4 months (range 1.8-229.1). The factors that significantly increased the risk of DMs were the presence of local recurrence (p=0.0001, OR:17.32, 95% CI:4.86-19.90), pathologically positive neck (p=0.008, OR:5.97, 95% CI: 3.25-10.45), and primary tumor localized in oral cavity or lip (p=0.035, OR:2.6, 95% CI:1.43-4.65).
CONCLUSION: Patients with these factors should be considered candidates for adjuvant systemic treatment and evaluated for early detection of DMs during follow-up.

Peponi E, Katinioti K, Tasiou I, et al.
3D conformal radiotherapy in primary nasopharyngeal cancer: effectiveness and prognostic factors.
J BUON. 2015 Mar-Apr; 20(2):514-20 [PubMed] Related Publications
PURPOSE: To assess the efficacy and safety of using 3D conformal radiation therapy (3DCRT) to treat nasopharyngeal cancer (NPC) in a Caucasian cohort and evaluate factors with prognostic value.
METHODS: Between September 2001 and November 2012, 44 NPC patients with a mean age of 57 years underwent 3DCRT at the University Hospital of Ioannina. Nineteen patients (43%) presented with WHO type 1 and 2 histology. Thirty two patients (73%) had advanced-stage disease (stage III/IV). Thirty-one patients (70%) received chemotherapy. The mean total radiotherapy dose prescribed to the planning target volume (PTV) was 67.2 Gy. The daily dose was 1.8 Gy.
RESULTS: With a median follow up of 43 months (range 8.4-125), the 4-year local relapse-free (LRFS), nodal relapse-free (NRFS), distant metastases-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were 90, 87, 91, 80 and 82%, respectively. Histology was a significant prognostic factor concerning overall survival, with worst prognosis in patients with WHO type 1/2 compared to type 3. Age <70 years, absence of retropharyngeal lymph node metastasis, complete response after treatment and the completion of ≥4 cycles of concurrent weekly cisplatin favored overall survival. Fifteen patients (34%) developed grade 3 late side effects (xerostomia: 6, soft tissue fibrosis: 6, hearing loss: 2, brachial plexus neuralgia: 1).
CONCLUSION: 3DCRT in our Caucasian cohort, characterized by predominantly advanced-stage disease, combined with chemotherapy, is an effective treatment modality approach in patients with NPC with excellent tolerance.

Jin NY, Wang K, Wei SQ, et al.
Diagnostic value of autofluorescence imaging combined with narrow band imaging in intraepithelial neoplasia of Barrett's esophagus.
J BUON. 2015 Mar-Apr; 20(2):399-405 [PubMed] Related Publications
PURPOSE: To evaluate the diagnostic values of Auto Fluorescence Imaging (AFI) combined with Narrow Band Imaging (NBI) in the diagnosis of the intraepithelial neoplasia of Barrett's esophagus (BE).
METHODS: Seventy four suspicious BE intraepithelial lesions were assessed in 50 patients by AFI, who were further subjected to NBI mode to observe the changes of gastric mucosal capillaries and gastric pits. The corresponding lesions were biopsied for pathological examination.
RESULTS: Among the 74 AFI-diagnosed cases of suspicious lesions, 44 (59.5%) were high-grade intraepithelial neoplasias (BEHGIN), while the remaining 30 cases (40.5%) were false-positive. The NBI-diagnostic results of these 44 BEHGIN lesions were as follows: 39 cases were confirmed and 5 were suspicious; among the 30 false-positive BEHGIN cases, NBI gave 7 false-positive cases. The false-positive rates decreased from 40.5% of AFI to 9.5% (7/74) of NBI-AFI (p<0.05). The positive predictive value of AFI in BEHGIN was 59.5% (44/74), while that of AFI-NBI combination was 84.8% (39/46; p<0.05).
CONCLUSIONS: The AFI-NBI combination technology could significantly improve (p<0.05) the detection rate of BEHGIN.

Hou PY, Teng CJ, Chung CS, et al.
Aortic pseudoaneurysm formation following concurrent chemoradiotherapy and metallic stent insertion in a patient with esophageal cancer.
Medicine (Baltimore). 2015; 94(20):e862 [PubMed] Related Publications
Aortic pseudoaneurysm formation subsequent to concurrent chemoradiotherapy (CCRT) for esophageal cancer patient with esophageal metallic stent insertion is a rare condition.A 52-year-old man with esophageal cancer, cT4N1M0, stage IIIC, was treated with concurrent weekly cisplatin (30 mg/m) and 5-Fluorouracil (500 mg/m) as well as radiotherapy (50.4 Gy in 28 fractions) for 6 weeks. An esophageal metallic stent was inserted for dysphagia 1 week after initiation of CCRT. During the treatment regimen, the platelet count dropped to less than 200 × 10 /μL. One month after the completion of CCRT, chest CT revealed the presence of an aortic pseudoaneurysm as well as aortoesophageal fistulas. A thoracic aortic endografting was performed and the patient responded well to surgery. However, the patient died 2 months later due to a nosocomial infection.Multimodality treatment for esophageal cancer comprising cisplatin-based CCRT and esophageal metallic stent placement near a great vessel may increase the risk of pseudoaneurysm formation.

Zhang W, Chen Y, Chen L, et al.
The clinical utility of plasma Epstein-Barr virus DNA assays in nasopharyngeal carcinoma: the dawn of a new era?: a systematic review and meta-analysis of 7836 cases.
Medicine (Baltimore). 2015; 94(20):e845 [PubMed] Related Publications
In this study, we assessed the potential of plasma Epstein-Barr virus (EBV) DNA assays to predict clinical outcomes in a large sample of nasopharyngeal carcinoma (NPC) patients and proposed a risk stratification model based on standardized EBV DNA load monitoring.We conducted a meta-analysis of 14 prospective and retrospective comparative studies (n = 7 836 patients) to evaluate the correlation between pretreatment plasma EBV DNA (pre-DNA), midtreatment plasma EBV DNA (mid-DNA), posttreatment plasma EBV DNA (post-DNA), the half-life value of plasma EBV DNA clearance rate (t1/2), and clinical outcomes. Our primary endpoint was overall survival (OS). Our secondary endpoints were progression-free survival (PFS), distant-metastasis-free survival (DMFS), and local-regional-failure-free survival (LRFS).High pre-DNA, detectable mid-DNA, detectable post-DNA, and slow EBV DNA clearance rates were all significantly associated with poorer OS, with hazard radios (HRs) equal to 2.81, 3.29, 4.26, and 3.58, respectively. Pre-DNA, mid-DNA, and post-DNA had the same effects on PFS, DMFS, and LRFS.Plasma EBV DNA assays are highly prognostic of long-term survival and distant metastasis in NPC patients. Based on the results of this meta-analysis, we propose a 4-grade systematic risk stratification model. Given the inherent limitations of the included studies, future well-designed randomized clinical trials are required to confirm to the findings of this analysis and to contribute to the development of individualized treatment strategies for NPC patients.

Guo Q, Pan J, Zong J, et al.
Suggestions for lymph node classification of UICC/AJCC staging system: a retrospective study based on 1197 nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy.
Medicine (Baltimore). 2015; 94(20):e808 [PubMed] Related Publications
This article provides suggestions for N classification of Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system of nasopharyngeal carcinoma (NPC), purely based on magnetic resonance imaging (MRI) in intensity-modulated radiation therapy (IMRT) era.A total of 1197 nonmetastatic NPC patients treated with IMRT were enrolled, and all were scanned by MRI at nasopharynx and neck before treatment. MRI-based nodal variables including level, laterality, maximal axial diameter (MAD), extracapsular spread (ECS), and necrosis were analyzed as potential prognostic factors. Modifications of N classification were then proposed and verified.Only nodal level and laterality were considered to be significant variables affecting the treatment outcome. N classification was thus proposed accordingly: N0, no regional lymph node (LN) metastasis; N1, retropharyngeal LNs involvement (regardless of laterality), and/or unilateral levels I, II, III, and/or Va involvement; N2, bilateral levels I, II, III, and/or Va involvement; and N3, levels IV, Vb, and Vc involvement. This proposal showed significant predicting value in multivariate analysis. N3 patients indicated relatively inferior overall survival (OS) and distant metastasis-free survival (DMFS) than N2 patients; however, the difference showed no statistical significance (P = 0.673 and 0.265 for OS and DMFS, respectively), and this was considered to be correlated with the small sample sizes of N3 patients (79 patients, 6.6%).Nodal level and laterality, but not MAD, ECS, and necrosis, were considered to be significant predicting factors for NPC. The proposed N classification was proved to be powerfully predictive in our cohort; however, treatment outcome of the proposed N2 and N3 patients could not differ significantly from each other. This insignificance may be because of the small sample sizes of N3 patients. Our results are based on a single-center data, to develop a new N classification that is universally acceptable; further verification by data from multicenter is warranted.

Bogaards JA, Wallinga J, Brakenhoff RH, et al.
Direct benefit of vaccinating boys along with girls against oncogenic human papillomavirus: bayesian evidence synthesis.
BMJ. 2015; 350:h2016 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: To assess the reduction in the vaccine preventable burden of cancer in men if boys are vaccinated along with girls against oncogenic human papillomavirus (HPV).
DESIGN: Bayesian evidence synthesis approach used to evaluate the impact of vaccination against HPV types 16 and 18 on the burden of anal, penile, and oropharyngeal carcinomas among heterosexual men and men who have sex with men. The reduced transmission of vaccine-type HPV from vaccination of girls was assumed to lower the risk of HPV associated cancer in all men but not to affect the excess risk of HPV associated cancers among men who have sex with men.
SETTING: General population in the Netherlands.
INTERVENTION: Inclusion of boys aged 12 into HPV vaccination programmes.
MAIN OUTCOME MEASURES: Quality adjusted life years (QALYs) and numbers needed to vaccinate.
RESULTS: Before HPV vaccination, 14.9 (95% credible interval 12.2 to 18.1) QALYs per thousand men were lost to vaccine preventable cancers associated with HPV in the Netherlands. This burden would be reduced by 37% (28% to 48%) if the vaccine uptake among girls remains at the current level of 60%. To prevent one additional case of cancer among men, 795 boys (660 to 987) would need to be vaccinated; with tumour specific numbers for anal, penile, and oropharyngeal cancer of 2162, 3486, and 1975, respectively. The burden of HPV related cancer in men would be reduced by 66% (53% to 805) if vaccine uptake among girls increases to 90%. In that case, 1735 boys (1240 to 2900) would need to be vaccinated to prevent an additional case; with tumour specific numbers for anal, penile, and oropharyngeal cancer of 2593, 29107, and 6484, respectively.
CONCLUSIONS: Men will benefit indirectly from vaccination of girls but remain at risk of cancers associated with HPV. The incremental benefit of vaccinating boys when vaccine uptake among girls is high is driven by the prevention of anal carcinomas, which underscores the relevance of HPV prevention efforts for men who have sex with men.

Wang F, Li S, Wang L, et al.
DATS suppresses growth of esophageal squamous cell carcinoma by regulation of ERK1/2.
Clin Lab. 2015; 61(3-4):315-22 [PubMed] Related Publications
BACKGROUND: It is well known that garlics contain a large number of organosulfur compounds including diallyl trisulfide (DATS), which possess anticancer properties. However, the effects of DATS on esophageal squamous cell carcinoma (ESCC) growth are still poorly understood. In this study, we investigated the effects of DATS on ESCC cell growth in vivo and in vitro, as well as the associated signaling pathways.
METHODS: Cell proliferation was measured using the crystal violet assay. The transwell method was used to evaluate the effect of DATS on ESCC cell migration. Also, Western blot was performed to detect the activation of ERK1/2 and AKT1 responds to DATS. Finally, the effect of DATS on ESCC xenografts in nude mice was also investigated.
RESULTS: Our results showed that DATS significantly inhibited ESCC cell proliferation in a time- and dose-dependent manner. DATS time-dependently (p < 0.05) increased phosphorylation of ERK1/2, but not AKT1. Suppression of ERK1/2 activation with PD9805 also completely blocked DATS-inhibited ESCC cell proliferation. Meanwhile, DATS also robustly suppressed ESCC xenograft growth and increased ERK1/2 activation in nude mice.
CONCLUSIONS: Our finding demonstrated that DATS inhibits the proliferation of ESCC cells by activation of ERK1/2 in vitro and in vivo. These findings revealed that DATS could be used for therapeutic intervention for human ESCC.

Griffith CC, Pai RK, Schneider F, et al.
Salivary gland tumor fine-needle aspiration cytology: a proposal for a risk stratification classification.
Am J Clin Pathol. 2015; 143(6):839-53 [PubMed] Related Publications
OBJECTIVES: Fine-needle aspiration (FNA) is useful in the evaluation of salivary gland tumors, but currently no standard terminology or risk stratification model exists.
METHODS: FNA smears were reviewed and categorized based on cytonuclear features, stromal characteristics, and background characteristics. Risk of malignancy was calculated for each category. Classifications as benign, neoplasm of uncertain malignant potential (NUMP), suspicious for malignancy, and positive for malignancy were used to aggregate categories into similar risk groups.
RESULTS: Categorization of salivary gland aspirates into morphologic categories resulted in the expected risk stratification. Grouping of categories maintained risk stratification, providing classes with malignancy risk as follows: benign, 2%; NUMP, 18%; suspicious for malignancy, 76%; and positive for malignancy, 100%.
CONCLUSIONS: Salivary gland FNA categorization into commonly encountered morphologic categories provides risk stratification, which translates to a simplified classification scheme of benign, NUMP, suspicious, and positive for malignancy similar to the paradigm in other organ systems.

Chernock RD, Hagemann IS
Molecular pathology of hereditary and sporadic medullary thyroid carcinomas.
Am J Clin Pathol. 2015; 143(6):768-77 [PubMed] Related Publications
OBJECTIVES: Medullary thyroid carcinoma (MTC) is a relatively uncommon type of thyroid malignancy, with unique histologic features and molecular pathology. It is important to recognize, because its management, which is in part driven by the genetic basis of this disease, is different from follicular-derived thyroid tumors. The aim of this article is to briefly review the histopathologic features of MTC and then explore its molecular pathology, including the role of molecular diagnostic testing and the use of targeted therapy for advanced disease.
METHODS: A review of published literature was performed.
RESULTS: A subset of MTC cases is hereditary and due to germline mutations in the RET tyrosine kinase receptor gene. Somatic mutations in either RET or RAS are also present in most sporadic tumors.
CONCLUSIONS: Molecular genetic testing is routinely performed to identify hereditary cases. In addition, understanding the molecular basis of both hereditary and sporadic MTC has led to the development of targeted therapy with tyrosine kinase inhibitors. Although additional data are needed, tumor mutation status may affect response to targeted therapy. Therefore, it is possible that genetic testing of tumor tissue to predict treatment response, as is currently done for other cancer types, may come into practice in the future.

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